SUMMARY Tissue engineering is rapidly developing, but remains limited by (i) scaffold and bioreactor designs that are based on predetermined parameters, and (ii) the lack of real-time, nondestructive measurements of cell and tissue function. To overcome these two limitations, we will develop adaptive-responsive biomaterials that can sense environmental signals and actuate the cells, and imaging-enabled bioreactors with real-time spatiotemporal control of engineered tissues with feedback from the measured cell responses. Our goal is to offer these advances to the tissue engineering community, and translate them into clinic. The proposed Tissue Engineering Resource Center brings together four highly productive and actively collaborating investigators from Columbia University (lead institution), Tufts University and Columbia University Medical Center-Presbyterian Hospital. An Administrative Board will coordinate the Center's activities, in conjunction with an External Advisory Committee, formed from the world leaders in tissue engineering and clinical translation that will evaluate the Center and provide guidance in strategic planning. The Center will partner with a number of existing resources (please see 13 letters of collaboration), and will have very generous financial support of the Columbia University School of Engineering ($2,425,000 over the five-year cycle). Strong and effective leadership is uniquely suited to support this transformative Center. The technical components of the Center are three Technology Research and Development Projects (TRD1: Adaptive-responsive biomaterials; TRD2: Imaging enabled bioreactor systems; TRD3: Regenerative engineering), eight Collaborative Projects and six Service Projects. We also propose a robust and diverse Training and Dissemination program to provide links between the projects in the Center with training of biomedical investigators in the use of new technologies, and the outreach to students, general public and underserved communities. Our mission is is that the Center will serve as a transformative driving force for the field of tissue engineering, by developing and translating new technologies, providing training and service, and offering dissemination and outreach programs for general public and high school students. With a highly innovative scientific premise, extensive foundational research, strong leadership and institutional support, experience in translational research, and long history of collaboration among the lead investigators, we are confident that the Center will accomplish its mission.